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Benefits of Human Milk Oligosaccharides on immune-dependent Diseases

At birth, babies’ immune system is not as strong as that of adults; it is still developing, which make the infants susceptible to immune-dependent diseases, such as allergies.1,2 Human breast milk is nature's most perfect source of nutrition providing all the necessary nutrients for babies’ healthy growth and development.3-6 Breastfeeding has several established benefits on child health, including immune-dependent benefits.3,7 Hence, breast milk plays a vital role in the development of mature immune responses during early life.8-10 Among the many different elements of human breast milk, human milk oligosaccharides (HMOs) are the third largest solid component.11,12 HMOs are synthesised by the mammary gland, with mean levels between 10 and 15 g/L in mature human breast milk.11,12

HMOs provide unique immune benefits to the baby.11,13,14 HMOs directly modulate gut mucosal immunity.11,15 In an experimental study, 2'-fucosyllactose (2’FL) and 6'-sialyllactose (6’SL) modulated human epithelial cell responses that were associated with allergic disease.16 HMOs may also have direct effects on systemic immunity,11 as a small part of HMOs reach systemic circulation.17Furthermore, HMOs indirectly support immunity by shaping the developing gut microbiota of infants,11,18 which has become an important aspect of human health.8,19-21 Clinical studies suggest that disturbances in the intestinal microbiota early in life, caused by caesarean delivery or early antibiotic exposure, contribute to the development of immune-mediated diseases, such as allergies or type 1 and 2 diabetes.8,20,22,23 In preclinical studies, the oral use of 2’FL significantly reduced food allergy symptoms,24 and providing HMOs has shown to delay or prevent the onset of type 1 diabetes.25

First promising evidence from observational clinical studies point towards a role of HMOs in immune-dependent diseases, such as atopic dermatitis or food allergy.26-28 Infants at risk of allergies, who were born by caesarean section, had a delayed onset of immunoglobulin (Ig) E-mediated eczema when fed human milk with higher levels of 2’-fucosylated HMOs, such as 2’FL.26 In another cohort study, infants who received human milk with low lacto-N-fucopentaose (LNFP) III levels were more likely to experience cow's milk allergy compared to those who received high LNFP III-containing milk.27 In a subgroup of a another cohort study, a certain profile of 10 HMOs in human breast milk, rather than individual or total HMOs, was associated with food sensitisation in the first year of life.28

Professor Hania Szajewska, Department of Paediatrics of the Medical University of Warsaw, Poland


Presented data suggest that the specific HMO profile in mother’s milk may help to reduce food sensitisation in her baby. Although food sensitisation is not necessarily a proof of an allergy, it may be considered as an important clinical indicator and predictor of future allergic disease. The exact mechanism how specific HMOs may help reduce the risk of allergy remains to be explored. Among the many ways how HMOs can influence immunity, HMOs contribute to the development of healthy gut microbiota, by acting as prebiotics. Alterations in the gut microbiota (dysbiosis) is known to play a role in allergy diseases. So far, no individual HMO has been associated with food sensitisation; however, it is likely that not all HMOs are equal.

Another interesting finding is the effect observed in children born by caesarean section. The rate of caesarean sections is increasing both in developed and developing countries. Recent studies confirm different colonisation patterns in infants born by caesarean delivery compared with infants born by vaginal delivery, which may persist beyond infancy. The exact effects of those differences on children’s health are still to be evaluated. Yet, evidence exists that it may increase the risk of specific diseases, including allergy.

References

1.Renz H, Adkins BD, Bartfeld S, et al. The neonatal window of opportunity-early priming for life. J Allergy Clin Immunol. 2018;141(4):1212-14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214658/pdf/nihms-994112.pdf
2.Abrahamsson TR, Sandberg Abelius M, Forsberg A, Bjorksten B, Jenmalm MC. A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization. Clin Exp Allergy. 2011;41(12):1729-39. https://www.ncbi.nlm.nih.gov/pubmed/21801246">
3.Victora CG, Bahl R, Barros AJ, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016;387(10017):475-490. https://reader.elsevier.com/reader/sd/pii/S0140673615010247?token=A866EC03C0080F1A2A64C7B73168149AEAE560FEDEDCA929EFB6A2948145F904E4975D7C465
18B87E19D5B16AA36A0AB

4.Breastfeeding AAP. Policy statement: breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827-41. https://pediatrics.aappublications.org/content/pediatrics/129/3/e827.full.pdf  
5.Agostoni C, Braegger C, Decsi T, et al. Breast-feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2009;49(1):112-25. http://www.espghan.org/fileadmin/user_upload/guidelines_pdf/Hep_Nutr/Breastfeeding.pdf
6.World Health Organisation. Infant and young child feeding: model chapter for textbooks for medical students and allied health professional. 2009. https://apps.who.int/iris/bitstream/handle/10665/44117/9789241597494_eng.pdf;
jsessionid=FAC1F52CA4AB80BD83E3018DBDA04805?sequence=1
7.Greer FR, Sicherer SH, Burks AW, Committee On N, Section On A, Immunology. The effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, hydrolyzed formulas, and timing of introduction of allergenic complementary foods. Pediatrics. 2019;143(4). https://pediatrics.aappublications.org/content/pediatrics/143/4/e20190281.full.pdf
8.van den Elsen LWJ, Rekima A, Verhasselt V. Early-Life Nutrition and Gut Immune Development. Nestle Nutr Inst Workshop Ser. 2019;90:137-49. https://www.ncbi.nlm.nih.gov/pubmed/?term=van+den+Elsen+LWJ%2C+Rekima+A%2C+Verhasselt+V
9.Rajani PS, Seppo AE, Jarvinen KM. Immunologically active components in human milk and development of atopic disease, with emphasis on food allergy in the pediatric population. Front Pediatr. 2018;6:218. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090044/
10.Collado MC, Cernada M, Bauerl C, Vento M, Perez-Martinez G. Microbial ecology and host-microbiota interactions during early life stages. Gut Microbes. 2012;3(4):352-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463493/pdf/gmic-3-352.pdf
11.Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406618/pdf/cws074.pdf
12.Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci USA. 2011;108 (Suppl 1):4653-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063602/pdf/pnas.201000083.pdf
13.Kunz C, Rudloff S. Compositional analysis and metabolism of human milk oligosaccharides in infants. Nestle Nutr Inst Workshop Ser. 2017;88:137-47. https://www.ncbi.nlm.nih.gov/pubmed/28346931
14.Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000;20:699-722. https://www.ncbi.nlm.nih.gov/pubmed/10940350
15.Donovan SM, Comstock SS. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann Nutr Metab. 2016;69 (Suppl 2):42-51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392703/pdf/nihms-1011209.pdf
16.Zehra S, Khambati I, Vierhout M, Mian MF, Buck R, Forsythe P. Human milk oligosaccharides attenuate antigen-antibody complex induced chemokine release from human intestinal epithelial cell lines. J Food Sci. 2018;83(2):499-508. https://www.ncbi.nlm.nih.gov/pubmed/?term=Human+milk+oligosaccharides+attenuate+antigen-antibody+complex+induced+chemokine+release+from+human+intestinal+epithelial+cell+lines
17.Rudloff S, Kunz C. Milk oligosaccharides and metabolism in infants. Adv Nutr. 2012;3(3):398S-405S. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649476/pdf/398S.pdf
18.Vandenplas Y, Berger B, Carnielli VP, et al. Human milk oligosaccharides: 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) in infant formula. Nutrients. 2018;10(9):1161. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164445/pdf/nutrients-10-01161.pdf
19.Moossavi S, Miliku K, Sepehri S, Khafipour E, Azad MB. The Prebiotic and Probiotic Properties of Human Milk: Implications for Infant Immune Development and Pediatric Asthma. Front Pediatr. 2018;6:197. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095009/pdf/fped-06-00197.pdf
20.Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science. 2016;352(6285):539-544. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050524/pdf/nihms820036.pdf
21. Rodriguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315782/pdf/MEHD-26-26050.pdf
22Isolauri E, Rautava S, Salminen S, Collado MC. Early-life nutrition and microbiome development. Nestle Nutr Inst Workshop Ser. 2019;90:151-162. https://www.ncbi.nlm.nih.gov/pubmed/30865983
23.Milani C, Duranti S, Bottacini F, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. 2017;81(4). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706746/
24.Castillo-Courtade L, Han S, Lee S, Mian FM, Buck R, Forsythe P. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model. Allergy. 2015;70(9):1091-102. https://www.ncbi.nlm.nih.gov/pubmed/?term=Attenuation+of+food+allergy+symptoms+following+treatment+with+human+milk+oligosaccharides+
in+a+mouse+model

25.Xiao L, Van't Land B, Engen PA, et al. Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice. Sci Rep. 2018;8(1):3829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832804/pdf/41598_2018_Article_22052.pdf
26.Sprenger N, Odenwald H, Kukkonen AK, Kuitunen M, Savilahti E, Kunz C. FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk. Eur J Nutr. 2017;56(3):1293-301. https://helda.helsinki.fi/bitstream/handle/10138/236702/10.1007_s00394_016_1180_6.pdf;j
sessionid=717EA360D0D59C4A2DA0CBEBFD27E681?sequence=1

27.Seppo AE, Autran CA, Bode L, Jarvinen KM. Human milk oligosaccharides and development of cow's milk allergy in infants. J Allergy Clin Immunol. 2017;139(2):708-11 e705. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303147/pdf/nihms-820545.pdf
28.Miliku K, Robertson B, Sharma AK, et al. Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study. Allergy. 2018;73(10):2070-73. https://www.ncbi.nlm.nih.gov/pubmed/?term=Human+milk+oligosaccharide+profiles+and+food+sensitization+among+infants+in+the+CHILD+Study



 

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